Neurodegenerative diseases are characterized by a progressive neurodegenerative process in which neuron structure and/or function are lost over time. Among the most common and most severe neurodegenerative diseases are amyotrophic lateral sclerosis, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Though genetic characteristics have been linked to some neurodegenerative diseases, the precise causes of most neurodegenerative diseases remain unclear. Further, effective treatments remain elusive for nearly all forms of neurodegenerative disease.
Parkinson's disease results from the death of dopamine-producing cells in the brain, and its primary motor symptoms arise from the loss of dopaminergic innervation in the striatum. The gold standard for treating Parkinson's is thus a neurotransmitter replacement strategy (levodopa, “L-DOPA”) aimed at restoring dopaminergic signaling and improving motor function. The use of L-DOPA, however, frequently results in the formation of a series of severely debilitating hyperkinetic movements termed levodopa-induced dyskinesias (LIDs). The molecular etiology underlying LIDs is poorly understood. Although the discontinuous administration of levodopa is thought to be a triggering event, it remains unclear why certain individuals are refractory to the L-DOPA-mediated induction of dyskinesias.